System comprising a nozzle and a fixing means therefor

ABSTRACT

The invention relates to a nozzle system for a delivery device for liquids, wherein the nozzle system comprises a nozzle and a device which fixes the nozzle in the delivery device. The delivery device, an atomiser, has a liquid reservoir from which a liquid is forced through the nozzle under pressure. The nozzle fixing means may itself be secured by a second fixing, e.g., in the form of a check nut, or the fixing may itself be a check nut. According to the invention the fixing means on the nozzle outlet side has a specific geometry which minimises the proportion of dispensed liquid deposited on the fixing means.  
     Preferably, the present invention is part of a propellant-free device for nebulising pharmaceutical liquids.

RELATED APPLICATIONS

[0001] Benefit of U.S. Provisional Application Serial No. 60/382,129,filed on May 21, 2002 is hereby claimed.

FIELD OF THE INVENTION

[0002] The invention relates to a nozzle system for a delivery devicefor liquids, wherein the nozzle system comprises a nozzle and a devicewhich fixes the nozzle in the delivery device. The delivery device, anatomiser, has a liquid reservoir from which a liquid is forced throughthe nozzle under pressure. The nozzle fixing means may itself be securedby a second fixing, e.g., in the form of a check nut, or the fixing mayitself be a check nut. According to the invention the fixing means onthe nozzle outlet side has a specific geometry which minimises theamount of dispensed liquid deposited on the fixing means.

[0003] Preferably, the present invention is part of a propellant-freedevice for nebulising pharmaceutical fluids. A nebuliser according tothe invention is used, for example, to produce an aerosol of dropletsfor inhalation through the mouth and pharyngeal cavity into the lungs ofa patient, for nasal administration or for spraying the surface of theeye.

PRIOR ART

[0004] WO 91/14468 discloses an apparatus for propellant-freeadministration of a metered quantity of a liquid pharmaceutical forapplication by inhalation. A further development of the device isdescribed in detail in WO 97/12687. Reference is specifically made tothese publications and the technology described therein is referred towithin the scope of the present invention as Respimat® technology. Thisterm refers in particular to the technology which forms the basis for adevice according to FIGS. 6a and 6b of WO 97/12687 and the associateddescription. Propellant-free liquids can easily be atomised using suchdevices.

[0005] In an inhaler of this kind liquid pharmaceutical formulations arestored in a reservoir. From there, they are conveyed through a risertube into a pressure chamber from where they are forced through anozzle.

[0006] The nozzle is held by a nozzle holder and the latter is securedby a check nut. The check nut has a liquid inlet side and a liquidoutlet side. On the liquid inlet side is an opening through which aliquid from the pressure chamber can enter the nozzle. On the oppositeside, the end face of the nozzle, the liquid then passes through twonozzle apertures which are aligned so that the jets of liquid leavingthe apertures strike one another and are thereby atomised. The nozzleapertures are arranged in the inhaler in such a way that they are indirect contact with the outer environment.

[0007] This is achieved by the fact that the entire region of the nozzleholder and check nut which is located above the nozzle apertures has arecess (or hole or bore) through it which provides a pathway for a jetof liquid leaving the nozzle or an emerging aerosol to leave theatomiser through the mouthpiece.

[0008] In the region of this nozzle holder this recess is funnel-shapedwhile in the region of the check nut this recess is in the form of auniform cylinder. The transition between the nozzle holder and check nuthas a sharp edge so that the cross section of the recess is like an L inwhich the crossbar is inclined slightly downwards. The entire recess infront of the nozzle aperture, which is made up of the recess in thenozzle holder and the recess of the check nut, has a point ofdiscontinuity in the elbow region of this L: the recess expandsdiscontinuously, i.e., viewed from the base it first of all widens outand then bends sharply vertically in the region of the transition fromthe nozzle holder to the check nut. The vertical direction correspondsto the direction of spraying of the emerging liquid, i.e., theperpendicular to the outside of the nozzle (end face).

[0009] These inhalers normally deliver formulations based on water ormixtures of water and ethanol. They are able to nebulise a small amountof a liquid formulation in the therapeutically required dosage within afew seconds to produce an aerosol suitable for therapeutic inhalation.With the device, quantities of less than 100 microlitres can benebulised, e.g., with one spray actuation, to produce an aerosol with anaverage particle size of less than 20 microns so that the inhalable partof the aerosol corresponds to the therapeutically effective amount. Inthese nebulisers with Respimat® technology a pharmaceutical solution isconverted by high pressure up to 500 bar into a low-speed aerosol mistdestined for the lungs, which the patient can then breathe in.

[0010] A small amount of the liquid may be deposited from the outside asa film or as an accumulation of small droplets on the end face of thenozzle or on the end face of the fixing means for the nozzle or on theinside of the mouthpiece. This fraction of the liquid is also referredto as the mouthpiece fraction within the scope of this specification.This mouthpiece fraction reduces the amount of liquid dispensed, withthe result that the inhalable fraction of the quantity delivered isreduced by the mouthpiece fraction.

[0011] The amount of liquid deposited need not be constant in everyspray actuation but may depend on numerous factors such as the spatialorientation of the device during the aerosol production or the ambienttemperature, relative humidity, etc. This leads on the one hand to acertain variability, however minor, in the amount dispensed which isthen available for the patient to take in (delivered dose). Of thedelivered dose, some has such a small particle size that the particlescan be breathed deep into the lungs and this fraction is known as theinhalable fraction. However, the present specification does notexpressly differentiate between the inhalable fraction and the totalquantity of aerosol available for the patient to breathe in unlessotherwise stated or unless clearly apparent from the context.

[0012] The liquid deposited may also cause contamination of the outersurface of the nozzle system or of the mouthpiece, which may in turnaffect the pharmaceutical quality of the next aerosol mist.

[0013] Although these two effects are only slight in devices usingRespimat® technology it is important for reasons of quality control tominimise such effects.

[0014] It has now been found that in devices of this kind for dispensingliquids the proportion of liquid deposited on the outside of the nozzlesystem can be reduced by the particular geometry of the nozzle or nozzlefixing means. In fact, it has been found, surprisingly, that themouthpiece fraction can be reduced if the entire area above the nozzleaperture (i.e., the area through which the dispensed liquid “flies” onits way to the mouthpiece) is funnel-shaped and has no edges.

DESCRIPTION OF THE INVENTION

[0015] It is an objective of the invention to reduce the variability ofthe proportion of the liquid delivered by means of a device fordelivering pharmaceutical liquids, such as atomisers, inhalers, etc.

[0016] A further aim of the invention is to reduce the proportion ofliquid which is deposited, from an aerosol mist, on the device fordelivering the pharmaceutical liquid.

[0017] Thus, a further aim of the invention is to increase the inhalablefraction of the quantity delivered and to reduce the mouthpiecefraction.

[0018] A further aim is to optimise the quality of delivery of a liquidusing atomisers having the Respimat® technology.

DETAILED DESCRIPTION OF THE INVENTION

[0019] This objective is achieved by means of a nozzle system whichconsists of a nozzle having at least two nozzle apertures and a nozzleholder and optionally a check nut, wherein

[0020] the nozzle apertures formed on the end face of the nozzle or thenozzle channels opening into the nozzle apertures are arranged so thatthe jets leaving the nozzle apertures are aimed towards one another atan angle α,

[0021] the nozzle is arranged in the nozzle holder and this isoptionally fixed by a check nut located above it,

[0022] in the assembled state the nozzle holder or the check nut or bothextend at least partially into the area in front of the nozzleapertures,

[0023] and the nozzle system is characterised in that in the assembledstate

[0024] the nozzle holder or, if the nozzle system has a check nut, thenozzle holder together with the check nut has an inner recess,

[0025] which begins on the side adjacent to the end face of the nozzleand extends as far as the outside of the nozzle holder parallel theretoor, in the case of a check nut, as far as the outside thereof parallelto the end face of the nozzle,

[0026] which, viewed from the end face of the nozzle, widens outsteadily and continuously in the direction of the outside of the nozzleholder parallel thereto or, in the case of a check nut, the outside ofsaid check nut parallel thereto,

[0027] so that the recess opens up the area of the nozzle system betweenthe end face of the nozzle and the outside of the nozzle holder parallelthereto or, in the case of a check nut, the outside of said check nutparallel thereto, for a liquid emerging from the nozzle opening to passthrough, so that this liquid can emerge from the nozzle, unimpeded bythe nozzle holder and the check nut, if applicable, and can bedistributed in the surrounding area.

[0028] According to advantageous embodiments of the nozzle system, therecess is funnel-shaped, preferably conical in construction.

[0029] The expression “continuously widening recess” refers within thescope of the present invention to a surface the edge of which runscontinuously in cross section. This refers to the area which ismacroscopically visible. By “runs continuously” is meant that there areno gaps of more than 0.5 mm, preferably more than 0.1 mm.

[0030] In cross section the edge of this “continuously widening recess”is preferably in the form of a straight, elliptical, hyperbolic, convexor concave line. In any case the edge runs continuously. The recess alsowidens continuously and does not merge into a cylindrical area.

[0031] The region of the recess with the smallest diameter, the basepoint, is located on the side of the nozzle holder which is adjacent tothe end face of the nozzle.

[0032] The part of the recess with the largest diameter, the apex orvertex, is on the opposite side, i.e., the outside of the nozzle holderparallel to the end face of the nozzle or, in the case of a check nut,the outside of said check nut which is parallel thereto.

[0033] The small diameter of the recess is between 0.1 mm and 2 mm,preferably between 0.6 mm and 1.0 mm.

[0034] The larger diameter of the recess is between 3 mm and 10 mm,preferably between 5 mm and 8 mm.

[0035] The transition of the base end of the recess to the end face ofthe nozzle may be constructed as an edge or it may be continuous, asdefined above, i.e., with no edges.

[0036] In the system according to the invention a check nut is notnecessary if the nozzle holder itself takes on this function.

[0037] Preferably, the nozzle system has a check nut. In this case thetransition between the nozzle holder and the check nut is constructedwith no edges, i.e., the continuous run of the recess is uninterrupted.Preferably, there is no change in the gradient of the preferablyconically widening recess in this area.

[0038] As an aid to solving the problem posed, it is also possible tovary the spacings of the nozzle aperture and the angle of inclination atwhich jets of liquid are delivered from the nozzle apertures.

[0039] The present invention is based on nozzle systems as described,for example, in EP 0664733 or EP 1017469. These are preferably nozzlesconsisting of at least two superimposed plates, at least one of theplates having a second microstructure so that the superimposed platesdefine on one side a liquid inlet adjoining a channel system and/or afilter system which then opens into the liquid outlets.

[0040] Microstructured nozzled bodies of this kind are described forexample in WO 94/07607 or WO 99/16530. Another embodiment is disclosedin the German Patent application filed under No. 10216101.1. Referenceis hereby made to all the documents.

[0041] With regard to WO 94/07607 we refer particularly to FIG. 1 andthe associated description. The nozzle body consists, for example, oftwo sheets of glass and/or silicon firmly attached to one another, atleast one of these sheets having one or more microstructured channelswhich connect the nozzle inlet side to the nozzle outlet side. On thenozzle outlet side there may be at least one, preferably, according tothe invention, two round or non-round openings 2 to 10 microns deep and5 to 15 microns wide, the depth preferably being 4.5 to 6.5 microns andthe length preferably being 7 to 9 microns.

[0042] On the base part, on the flat surface, there may be a set ofchannels to create a plurality of filter routes (filter channels) incollaboration with the substantially flat surface of the top part. Thebase part may have a fill chamber the top of which is again formed bythe top part. This fill chamber may be provided before or after thefilter channels. It is also possible to have two fill chambers of thiskind. Another set of channels on the substantially flat surface of thebase part which is provided downstream of the filter channels forms,together with the top part, a set of channels which create a pluralityof nozzle outlet routes.

[0043] Preferably, the overall cross sectional area of the nozzleoutlets is 25 to 500 square micrometres. The total cross sectional areais preferably 30 to 200 square micrometres.

[0044] In another embodiment this nozzle construction has only onenozzle aperture.

[0045] In other embodiments of this kind the filter channels and/or thefill chamber are omitted.

[0046] Preferably, the filter channels are formed by projectionsarranged in a zigzag shape. Thus, for example, a zigzag configuration ofthis kind is formed by at least two rows of projections. A number ofrows of projections may also be formed, the projections being laterallyoffset from one another in order to construct additional rows which areskewed relative to these rows, these additional rows forming the zigzagconfiguration. In embodiments of this kind the inlet and outlet may eachhave a longitudinal slot for unfiltered or filtered fluid, each of theslots being substantially the same width as the filter and substantiallythe same height as the projections on the inlet and outlet sides of thefilter. The cross section of the throughflow passages formed by theprojections may be perpendicular to the direction of flow of the fluidand may decrease from row to row, viewed in the direction of flow. Also,the projections arranged closer to the inlet side of the filter may belarger than the projections arranged closer to the outlet side of thefilter. Additionally, the spacing between the base part and top part maytaper in the region from the nozzle inlet side to the nozzle outletside.

[0047] The zigzag configuration which is formed by the minimum of tworows of projections has an angle of inclination alpha of preferably 20°to 250°.

[0048] Further details of this nozzle construction may be found in WO94/07607. We hereby refer specifically to this publication, particularlyFIG. 1 and the associated description.

[0049] In embodiments of the nozzle having a plurality of nozzleapertures, preferably all of them are formed on a common side. In suchcases the nozzle apertures may be oriented so that the jets of liquidemerging from them meet in front of the nozzle aperture. Systems of thiskind require nozzles with at least two apertures. Nozzles of this kindare preferred according to the invention.

[0050] The nozzle may be embedded in an elastomeric sleeve as describedin WO 97/12683. In its simplest form a sleeve of this kind is a ring ormember having an opening into which the nozzle can be inserted. Thisopening surrounds the nozzle block over its entire outer surface, i.e.,the surface which is perpendicular to the preferably linear axis formedby the nozzle inlet side and the nozzle outlet side. The sleeve is openat the top and bottom so as not to impede either the supply of liquid tothe nozzle inlet side of the nozzle or the delivery of the liquid. Thissleeve may in turn be inserted in a second sleeve. The external form ofthe first sleeve is preferably conical. The opening of the second sleeveis shaped accordingly. The first sleeve may be made of an elastomer.

[0051] The nozzle is secured by the device according to the invention.

[0052] A nozzle of this kind, optionally including the sleeve, is partof a nozzle system by means of which the nozzle is held at a definedplace in the delivery device, preferably from outside in the directionof the hollow piston. According to the invention a nozzle system of thiskind therefore consists of a nozzle and a nozzle holder and optionally acheck nut. All the elements have an end face. This is the side which isoriented away from the side of the nozzle having the nozzle aperture,i.e., it faces outwards. The inside of the end face of the nozzle holderor the check nut may come into contact with the liquid outlet side ofthe nozzle and thereby exert the force needed to secure the nozzle inthe direction of the liquid inlet side of the nozzle. The end face ofthe nozzle holder and/or of the check nut has or have a through-bore orhole in the form of a recess through which the aerosol can escape fromthe nozzle. Therefore, the nozzle apertures are in, or in a direct linebelow, the bore or the recess.

[0053] The recess is preferably constructed as an inner recess whichwidens continuously from the nozzle apertures. Embodiments of the nozzlesystem wherein the recess is funnel-shaped, preferably conical, areadvantageous.

[0054] In nozzles having at least two nozzle apertures orientated sothat the two jets of liquid leaving the nozzle body meet, the point ofimpact, the point where the jets of liquid meet and are atomised to forman aerosol, is preferably located close to the base of the recess, i.e.,in the region of the nozzle aperture. It is obvious that in such a casethe recess is one of the areas particularly at risk of liquid beingdeposited thereon.

[0055] This invention is preferably used in a nebuliser of Respimat®technology, which is described in more detail hereinafter.

[0056] The preferred atomiser essentially comprises a lower and an upperhousing mounted to be rotatable relative to one another, the upper partof the housing containing a spring housing with spring which istensioned by rotating the two housing parts by means of a lockingclamping mechanism preferably in the form of a screw thread or gear andis released by pressing a release button on the upper part of thehousing. This moves a power take-off flange connected to a hollow pistonon the lower end of which a container can be fitted and at the upper endof which are found a valve and a pressure chamber which is connected forfluid transmission to the nozzle or the nozzle system formed in theupwardly open part of the upper housing part. The liquid is sucked in bythe hollow piston and pumped to the pressure chamber from where it isexpelled through the nozzle in the form of an aerosol.

[0057] The hollow piston with valve body corresponds to a devicedisclosed in WO 97/12687. It projects partially into the cylinder of thepump housing and is disposed to be axially movable in the cylinder.Reference is made particularly to FIGS. 1-4—especially FIG. 3—and theassociated parts of the description. At the moment of release of thespring the hollow piston with valve body exerts, at its high pressureend, a pressure of 5 to 60 Mpa (about 50 to 600 bar), preferably 10 to60 Mpa (about 100 to 600 bar) on the fluid, the measured amount ofactive substance solution.

[0058] The valve body is preferably mounted at the end of the hollowpiston which faces the nozzle body. The valve body is connected forfluid transmission with the nozzle. The delivery device also comprises alocking clamping mechanism. This contains a spring, preferably acylindrical helical compression spring, as a store for the mechanicalenergy. The spring acts on the power take-off flange as a spring memberthe movement of which is determined by the position of a locking member.The travel of the power take-off flange is precisely limited by an upperstop and a lower stop. The spring is preferably tensioned via astepping-up gear, e.g., a helical sliding gear, by an external torquewhich is generated when the upper housing part is turned relative to thespring housing in the lower housing part. In this case, the upperhousing part and the power take-off flange contain a single- ormulti-speed spline gear.

[0059] The locking member with the engaging locking surfaces is arrangedin an annular configuration around the power take-off flange. Itconsists for example of a ring of plastics or metal which is inherentlyradially elastically deformable. The ring is arranged in a planeperpendicular to the axis of the atomiser. After the tensioning of thespring, the locking surfaces of the locking member slide into the pathof the power take-off flange and prevent the spring from being released.The locking member is actuated by means of a button. The actuatingbutton is connected or coupled to the locking member. In order toactuate the locking clamping mechanism the actuating button is movedparallel to the annular plane, preferably into the atomiser, and thedeformable ring is thereby deformed in the annular plane. Details of theconstruction of the locking clamping mechanism are described in WO97/20590.

[0060] The lower housing part is pushed axially over the spring housingand covers the bearing, the drive for the spindle and the storagecontainer for the fluid.

[0061] When the atomiser is operated, the upper part of the housing isrotated relative to the lower part, the lower part taking the springhousing with it. The spring meanwhile is compressed and biased by meansof the helical sliding gear, and the clamping mechanism engagesautomatically. The angle of rotation is preferably a whole-numberfraction of 360 degrees, e.g., 180 degrees. At the same time as thespring is tensioned, the power take-off component in the upper housingpart is moved along by a given amount, the hollow piston is pulled backinside the cylinder in the pump housing, as a result of which some ofthe fluid from the storage container is sucked into the high pressurechamber in front of the nozzle.

[0062] If desired, a plurality of replaceable storage containerscontaining the fluid to be atomised can be inserted in the atomiser oneafter another and then used. The storage container contains thepropellant-free aerosol preparation.

[0063] The atomising process is initiated by gently pressing theactuating button. The clamping mechanism then opens the way for thepower take-off component. The biased spring pushes the piston into thecylinder in the pump housing. The fluid emerges from the nozzle of theatomiser in the form of a spray. The liquid pharmaceutical preparationhits the nozzle body at an entry pressure of up to 600 bar, preferably200 to 300 bar and is atomised through the nozzle openings into aninhalable aerosol. The preferred particle sizes of the aerosol are up to20 microns, preferably 3 to 10 microns. Volumes of 10 to 50 microlitresare preferably delivered, volumes of 10 to 20 microlitres are morepreferable, whilst a volume of 15 microlitres per spray is particularlypreferred.

[0064] The components of the atomiser (nebuliser) consist of a materialwhich is suited to its purpose. The housing of the atomiser and—insofaras the operation allows—other parts are also preferably made ofplastics, e.g., by injection moulding. For medical uses, physiologicallyharmless materials are used.

[0065] Preferably, a nebuliser according to the invention is cylindricalin shape and has a handy size of less than 9 to 15 cm long and 2 to 4 cmwide, so that it can be carried anywhere by the patient.

[0066] Further details of construction are disclosed in PCT applicationsWO 97/12683 and WO 97/20590, to which reference is made hereby.

[0067] The invention is hereinafter illustrated in more detail withreference to drawings.

FIGURES

[0068]FIG. 1: Graph for investigating nozzle systems with two nozzleapertures directed towards one another: dependency of the mouthpiecefraction (“deposition in the mouthpiece”) on the impact height h for anozzle system with a discontinuously expanding recess and for a nozzlesystem according to the invention with a conical recess,

[0069]FIG. 2: A graph for investigating nozzle systems with two nozzleapertures directed towards each other: dependency of the aerosol qualityon the height of impact,

[0070]FIG. 3: A graph for investigating nozzle systems with two nozzleopenings directed towards one another: dependency of the mouthpiecefraction and the quality of the inhalable fraction on the height ofimpact,

[0071]FIG. 4: A graph for investigating nozzle systems with two nozzleapertures directed towards one another: dependency of the mouthpiecefraction on the cone angle 2θ nozzle fixing systems with a conicalrecess,

[0072] FIGS. 5,6: Nozzles with two nozzle apertures directed towards oneanother: influence of the angle of impact a on the inhalable fractionand the mouthpiece fraction in nozzle fixing systems with a conicalrecess,

[0073]FIG. 7: A view of a first embodiment of a nozzle system in sideelevation, partially in section,

[0074]FIG. 8: A view of a second embodiment of a nozzle system in sideelevation, partly in section,

[0075]FIG. 9: A diagrammatic view of a nozzle system according to theinvention in side elevation, in section,

[0076]FIG. 10: A diagrammatic view of an embodiment of a nozzle memberin side elevation, in section,

[0077]FIGS. 11a/b: Diagram of the Respimat® type nebuliser.

[0078]FIG. 1 shows the dependency of the mouthpiece fraction(“deposition in the mouthpiece”) on the height of impact h for a nozzlesystem with a discontinuously expanding recess (A) and for a nozzlesystem according to the invention with a conical recess (B). This graphshows the dependency of the mouthpiece fraction on the height of impact.Accordingly, the mouthpiece fraction can be reduced by increasing theheight of impact h.

[0079]FIG. 1 also shows that the special construction of the nozzlesystem according to the invention in the region in front of the nozzleapertures leads to a substantial reduction in the mouthpiece fractioncompared with conventional systems. Thus, for example, the mouthpiecefraction can be reduced from about 1.9 mg to 0.8 mg at an impact heighth=25 μm, corresponding to a reduction of about 60%.

[0080] The reduction in the mouthpiece fraction has two positiveeffects. On the one hand, by minimising the amount of mouthpiecefraction the quantity delivered is maximised, which in turn has afavourable effect on the inhalable fraction which consequently becomeslarger, in principle. This therefore crucially contributes to thesolution to one of the problems of the invention, namely of maximisingthe inhalable fraction.

[0081] Moreover, by reducing the mouthpiece fraction the effects ofvariability of the mouthpiece fraction are reduced. Because of the smallamount of mouthpiece fraction fluctuations in this amount result in onlyminor fluctuations in the quantity delivered and hence in the inhalablefraction. The inhalable fraction is now highly reproducible, i.e., ithas low variability. The problem of the inconstant mouthpiece fractionsubject to certain tolerances is now of only marginal importance. Thisalso solves the second problem on which the invention is based, namelyof ensuring high reproducibility, i.e., low variability, of theinhalable fraction.

[0082] However, what is crucial to the success of the nozzle systemaccording to the invention is that this single measure not onlyminimises the mouthpiece fraction but at the same time maximises theinhalable fraction.

[0083] It is found according to the invention that when reducing themouthpiece fraction in nozzle systems comprising nozzles with two nozzleapertures aligned so that the jets which emerge from them meet at apoint in front of the nozzle (point of impact), it is pointless toincrease the height of impact h on its own (FIG. 1). This is because thetwo jets actually have to meet, which requires the smallest possibleheight of impact h. Moreover, the jets are supposed to meet inconcentrated form before they fall as droplets. In addition it hassurprisingly been found that the magnitude of the height of impact halso affects the quality of atomisation and hence the inhalable fractionso that, as the height of impact h increases, the quality of atomisationor the inhalable fraction is reduced. Then, as the height of impact hincreases, there are a greater number of larger particles and fewersmall particles. This effect is illustrated in FIG. 2 in which theinhalable fraction is seen as the part which comprises particles with adiameter of less than 5.8 μm. Here again, the advantageous effect of thenozzle system according to the invention as against a nozzle system witha discontinuously expanding recess is apparent.

[0084]FIG. 3 shows the mouthpiece fraction in milligrams and theinhalable fraction in percent by volume (proportion by volume of theaerosol containing particles with diameters of less than 5.8 μm, asdetected by a laser beam) as a function of the height of impact h. Forexample, for an impact angle α=75° the mouthpiece fraction decreasesrapidly as the height of impact h increases. At the same time, however,the inhalable fraction, i.e., the quality of atomisation, is not reducedto the same extent.

[0085] If it is also remembered that not only is the quality ofatomisation—as characterised by the inhalable fraction in percent byvolume—positively affected but also the amount actually delivered isincreased by reducing the absolute quantity of the mouthpiece fraction,it will be apparent that the absolute inhalable fraction can beincreased substantially.

[0086] It has been found according to the invention that in advantageousembodiments of the nozzle system the recesses in front of the nozzleaperture are conical and have a cone angle 2θ in the range between 55°and 155°, preferably in the range between 70° and 140°. Particularlyfavourable are nozzle systems wherein the recess of conical constructionhas a cone angle 2θ which is in the range between 70° and 85° or in therange between 95° and 140°, especially in the range between 105° and125°.

[0087] The advantages of these embodiments will become apparent fromFIG. 4 which shows, in the form of a bar graph, the mouthpiece fractionin milligrams for different cone angles 2θ. All of the embodiments havea mouthpiece fraction of not more than 1.75 mg which is small comparedwith the prior art (cone angle 2θ=90°). The embodiments which have coneangles 2θ in the range from 70° to 85° or in the range between 95° and140°, particularly in the range between 105° and 125°, have even smallermouthpiece fractions. The minimum is obtained with a cone angle 2θ=110°.

[0088] According to another aspect the present invention relates toparticular nozzles which may advantageously be incorporated in thenozzle systems according to the invention. These nozzles arecharacterised in that the point of collision where the jets meet has aheight of impact h above the nozzle apertures in the range between 20 μmand 85 μm, preferably in the range between 25 μm and 75 μm. If theheight of impact is within the range specified, the various objectivescan all advantageously be met, by achieving in particular a lowmouthpiece fraction and reliable steering of the jets of liquid towardsone another whilst obtaining a high inhalable fraction.

[0089] Nozzles wherein the point of collision where the jets meet has aheight of impact h above the nozzle apertures in the range between 35 μmand 75 μm are advantageous. With the impact height in this range theparameters which influence one another are brought to an optimum level.

[0090] Embodiments of the nozzles wherein the angle α is in the rangefrom 50° to 110°, preferably from 65° to 95° and more particularly inthe range from 75° to 90° are advantageous.

[0091]FIGS. 5 and 6 show the effect of the angle of impact α on theinhalable fraction and the mouthpiece fraction. Both these fractionsincrease as the angle of impact α increases. With regard to the qualityof atomisation it is preferable for the jets to meet head-on ifpossible. Large angles ensure a high inhalable fraction, i.e., a highvolume proportion of small particles with diameters less than 5.8 μm inthe spray mist.

[0092] However, large angles α also lead to large mouthpiece fractionsat the same time. The free path along which the jets travel betweenleaving the nozzle apertures and meeting one another should not be toogreat, to ensure among other things that the jets do not disperse beforethe meeting point. If, however, the angle of impact α is increased, theheight of impact must be reduced to keep the free path of the jetsconstant. The effects of this measure have already been explained.However, even with a constant height of impact and enlargement of theangle, an increasing mouthpiece fraction is obtained as the particles ofthe spray mist are increasingly driven towards the nozzle system as theangle of impact increases, eventually resulting in a larger mouthpiecefraction. The angle regions mentioned above are best able to accommodatethe competing mechanisms.

[0093] In advantageous embodiments of the nozzles according to theinvention, the spacing a of the nozzle apertures is in the range from 40μm to 125 μm, preferably in the range from 50 μm to 115 μm, moreparticularly in the range from 60 μm to 105 μm.

[0094] Advantageous embodiments of the nozzle system are characterisedin that only the nozzle holder extends into the area in front of thenozzle apertures in the assembled state. This avoids any joints betweenthe nozzle holder and check nut in the region of the nozzle apertures.Joints are a particular problem in terms of the accumulation of aerosolparticles as, once deposited, any particles here are not generallyreleased again.

[0095] Two embodiments shown in FIGS. 7, 8, 9 and 10 illustrate theinvention in more detail.

[0096]FIG. 7 shows a first embodiment of the nozzle system 1 in sideelevation, partly in section.

[0097] The nozzle 3 or nozzle body as an independent constructionunit—so called uniblock—is disposed in a conical sleeve 6 which is inturn placed in the nozzle holder 4. The nozzle holder 4 is clamped tothe housing 7 by means of a check nut 2 and this secures the nozzle 3.

[0098] At the same time the check nut 2 engages from outside in thenozzle holder 4, although it does not extend into the area in front ofthe nozzle apertures. The recess 5 is conical in shape, in that itwidens out continuously as its distance from the nozzle aperturesincreases. The recess 5 has a cone angle 2θ, whilst FIG. 7 shows by wayof example a plurality of different cone angles, with the result thatthis Figure shows five different embodiments of the recess 5 and henceof the nozzle system 1, all basically the same. Specifically, it showscone angles 2θ of 70°, 80°, 90°, 100° and 110°.

[0099] Because the check nut 2 engages in the nozzle holder 4 fromoutside, the recess 5 is formed exclusively by the nozzle holder 4.

[0100] In contrast, FIG. 8 shows a second embodiment, again in sideelevation and partly in section, wherein both the nozzle holder 4 andthe check nut 2 extend into the area in front of the nozzle apertures.Otherwise, the nozzle system 1 shown in FIG. 8 corresponds to the nozzlesystem described above. The same reference numerals have been used forcorresponding components, and therefore we refer to the description ofFIG. 7 with regard to the components of similar construction.

[0101]FIG. 9 again shows a nozzle system 1 according to the invention.This comprises a recess 5 of conical shape. Unlike nozzle systems with adiscontinuously expanding recess, the recess 5 does not contain anysteps. Such steps may occur in particular in the area where the checknut engages in the nozzle holder. In such cases, particles of the spraymist may accumulate on the edges of the step and thus contribute to themouthpiece fraction.

[0102]FIG. 10 is a diagrammatic view of a detail of an embodiment of anozzle member 3 shown in sectional side view.

[0103] The two nozzle channels 9 are arranged so that the jets leavingthe nozzle apertures 11 of the nozzle channels meet at the point ofcollision 10 at an angle α=90°. The point of collision 10 has a heightof impact h=25 μm above the nozzle apertures.

[0104]FIG. 11a shows a longitudinal section through the atomiser withthe spring under tension, FIG. 11b shows a longitudinal section throughthe atomiser with the spring released.

[0105] The upper housing part (51) contains the pump housing (52), onthe end of which is mounted the holder (53) for the atomiser nozzle. Inthe holder is the expanding recess (54) and the nozzle body (55). Thehollow piston (57) fixed in the power take-off flange (56) of thelocking clamping mechanism projects partly into the cylinder of the pumphousing. At its end the hollow piston carries the valve body (58). Thehollow piston is sealed off by the gasket (59). Inside the upper housingpart is the stop (60) on which the power take-off flange rests when thespring is relaxed. Located on the power take-off flange is the stop (61)on which the power take-off flange rests when the spring is undertension. After the tensioning of the spring, the locking member (62)slides between the stop (61) and a support (63) in the upper housingpart. The actuating button (64) is connected to the locking member. Theupper housing part ends in the mouthpiece (65) and is closed off by theremovable protective cap (66).

[0106] The spring housing (67) with compression spring (68) is rotatablymounted on the upper housing part by means of the snap-fit lugs (69) androtary bearings. The lower housing part (70) is pushed over the springhousing. Inside the spring housing is the replaceable storage container(71) for the fluid (72) which is to be atomised. The storage containeris closed off by the stopper (73), through which the hollow pistonprojects into the storage container and dips its end into the fluid(supply of active substance solution).

[0107] The spindle (74) for the mechanical counter (optional) is mountedon the outside of the spring housing. The drive pinion (75) is locatedat the end of the spindle facing the upper housing part. On the spindleis the slider (76).

1. Nozzle system (1) which consists of a nozzle (3) having at least twonozzle apertures (11) and a nozzle holder (4) and optionally a check nut(2), wherein the nozzle apertures (11) or the nozzle channels (9)opening into the nozzle apertures (11) are arranged so that the jetsleaving the nozzle apertures (11) are aimed towards one another at anangle α, the nozzle (3) is arranged in the nozzle holder (4) and this isoptionally fixed by a check nut (2), in the assembled state the nozzleholder (4) or the check nut (2) or both extend at least partially intothe area in front of the nozzle apertures (11), characterised in that inthe assembled state the nozzle holder (4) or, if the nozzle system (1)has a check nut (2), the nozzle holder (4) together with the check nut(2) has an inner recess, which begins on the side adjacent to the endface of the nozzle (3) and extends as far as the outside of the nozzleholder (4) parallel thereto or, in the case of a check nut (2), as faras the outside thereof parallel to the end face of the nozzle, which,viewed from the end face of the nozzle (3), widens out steadily andcontinuously in the direction of the outside of the nozzle holder (4)parallel thereto or, in the case of a check nut (2), the outside of saidcheck nut parallel thereto.
 2. Nozzle system (1) according to claim 1,characterised in that a check nut (2) is provided.
 3. Nozzle system (1)according to claim 1, characterised in that the recess (5) isfunnel-shaped or conical.
 4. Nozzle system (1) according to claim 3,characterised in that the recess (5) of conical construction has a coneangle 2θ in the range between 55° and 155°.
 5. Nozzle system (1)according to claim 4, characterised in that the recess (5) of conicalconstruction has a cone angle 2θ in the range between 70° and 140°. 6.Nozzle system (1) according to claim 5, characterised in that the recess(5) of conical construction has a cone angle 2θ in the range between 70°and 85°.
 7. Nozzle system (1) according to claim 5, characterised inthat the recess (5) of conical construction has a cone angle 2θ in therange between 95° and 140°.
 8. Nozzle system (1) according to claim 7,characterised in that the recess (5) of conical construction has a coneangle 2θ in the range between 105° and 125°.
 9. Nozzle system (1)according to claim 1, characterised in that the point of collision (10)where the jets meet has a height of impact h above the nozzle apertures(11) which is in the range between 20 μm and 85 μm.
 10. Nozzle system(1) according to claim 9, characterised in that the point of collision(10) where the jets meet has a height of impact h above the nozzleapertures (11) which is in the range between 25 μm and 75 μm.
 11. Nozzlesystem (1) according to claim 10, characterised in that the point ofcollision (10) where the jets meet has a height of impact h above thenozzle apertures (11) which is in the range between 35 μm and 75 μm. 12.Nozzle system (1) according to claim 1, characterised in that the angleα is in the range between 50° and 110°.
 13. Nozzle system (1) accordingto claim 12, characterised in that the angle α is in the range between65° and 95°.
 14. Nozzle system (1) according to claim 13, characterisedin that the angle α is in the range between 75° and 90°.
 15. Nozzlesystem (1) according to claim 1, characterised in that the spacing a ofthe nozzle apertures (11) is in the range between 40 μm and 125 μm. 16.Nozzle system (1) according to claim 15, characterised in that thespacing a of the nozzle apertures (11) is in the range between 50 μm and115 μm.
 17. Nozzle system (1) according to claim 15, characterised inthat the spacing a of the nozzle apertures (11) is in the range between60 μm and 105 μm.
 18. Nozzle system (1) according to claim 1,characterised in that in the assembled state only the nozzle holder (4)extends into the area in front of the nozzle apertures (11).
 19. Nozzlesystem according to claim 1, characterised in that the nozzle is formedfrom at least two construction units.
 20. Nozzle system according toclaim 1, characterised in that the nozzle is formed from at least twosuperimposed plates, at least one of the plates having a secondmicrostructure so that the plates lying one on top of the other define,on one side, a liquid inlet connected to a channel system and/or afilter system which then opens into one or more liquid outlets. 21.Delivery device for liquids, characterised in that it comprises a nozzlesystem according to one of claim
 1. 22. Delivery device according toclaim 21, characterised in that it is an atomiser for pharmaceuticalliquids.
 23. Delivery device according to claim 21, characterised inthat the device comprises a lower and an upper housing part mounted tobe rotatable relative to one another, the upper part of the housingcontaining a spring housing with spring which is tensioned by rotatingthe two housing parts by means of a locking clamping mechanismpreferably in the form of a screw thread or gear and is released bypressing a release button on the upper part of the housing, the springmeanwhile moving a power take-off flange connected to a hollow piston onthe lower end of which a container can be fitted and at the upper end ofwhich are found a valve and a pressure chamber which is connected forfluid transmission to the nozzle or the nozzle system formed in theupwardly open part of the upper housing part.
 24. Delivery deviceaccording to claim 23, characterised in that the device is an inhaler orsome other atomiser for medicinal liquids.